The ability to incorporate two or more active ingredients in a single dosage form offers several advantages. The advantages include convenient delivery of multiple medications, avoidance of potential mistakes by user if many medications are to be taken at the same time, increased user compliance, possible synergistic effect and possible controlled delivery.
Various oral medications have been manufactured in the form of soft gelatin capsules. A liquid or semi-solid fill composition is typically encapsulated in soft gelatin capsules using the conventional rotary die method. However, the incorporation of two or more APIs in a soft gelatin capsule can result in chemical incompatibilities or reactions.
Attempts have been made to separate active ingredients to avoid chemical incompatibilities and to maintain the chemical stability of the different active ingredients. Physical barriers may be utilized to separate fill formulations containing different active ingredients. For example, a gelatin partition may be used to divide a soft gelatin capsule into separate chambers with each chamber containing a different fill formulation.
Further attempts have been made to incorporate two or more active ingredients by formulating the fill formulations so that they form different liquid phases or are incompatible. For example, two different fill formulations forming different liquid phases may be layered side-by-side in a soft gelatin capsule. The use of hydrophobic and hydrophilic fill formulations allows for the fill formulations to be layered side-by-side in a soft gelatin capsule. Soft gelatin fill formulations may also be formulated to incorporate API particles suspended in a liquid carrier.
Preformed solid dosage forms may be enrobed with a gelatin coating to permit easier swallowing of the dosage form. Enrobed solid dosage forms may incorporate a second active ingredient in the gelatin coating. A limitation of enrobed solid dosage forms is that they cannot accommodate a liquid phase.
There exists a need for soft gelatin dosage forms capable of providing single ingestion of multiple dosage forms, each having different phases. It is desirable to provide soft gelatin dosage forms containing a solid dosage form and liquid fill phase which maintains the chemical stability of each phase and prevents any chemical reaction between the multiple phases. It is also desirable to incorporate preformed solid dosage forms to retain the established pharmaceutical characteristics of the preformed solid dosage form in combination with a liquid phase, such as physical and chemical stability, active ingredient release profile of the solid dosage form, bioavailability and clinical performance.